The hypothalamic regulation of pituitary hormone secretion is exerted via peptide hormone transmitters that are released into the pituitary portal system and interact with specific high-affinity receptors in the individual cell types of the anterior pituitary gland. The major hypothalamic regulatory peptides include specific releasing factors for gonadotropins (GnRH) and corticotropin (CRF) and probably angiotensin II (AII), which is present in the hypothalamus and has been shown to bind to receptors in the anterior pituitary gland. In studies on the control of gonadotropin secretion, rat pituitary GnRH receptors were shown to be positively regulated by exogenous and endogenous GnRH, and to provide a useful index of endogenous GnRH secretion. GnRH agonist analogs were shown to activate pituitary cells in proportion to their receptor binding affinities, and were further characterized in gonadotrophs purified by unit gravity sedimentation and centrifugal elutriation. The previous finding of up-regulation of GnRH receptors was analyzed in cultured pituitary cells, and stimulation and desensitization by GnRH was studied in perifused pituitary cells. Further evidence for the role of phospholipid turnover and arachidonic acid metabolites in GnRH action was obtained in purified pituitary gonadotrophs. In such cells, increases in phosphatidylinositol and phosphatidic acid (PA) were found during GnRH action, and PA was shown to stimulate both cyclic GMP production and LH release. In the corticotroph, studies on the interaction between CRF, AII, and other regulators of cyclic AMP and corticotropin secretion were performed, and receptors for CRF were identified by binding analysis with radio-iodinated Tyr-CRF. The recently identified pituitary receptors for angiotensin II (AII) were shown to mediate the stimulatory effect of the octapeptide upon prolactin release in vitro, and to be co-enriched in lactotrophs purified by elutriation. These findings suggest that angiotensin II could serve as an additional hypothalamic regulator of pituitary function, and could contribute to the physiological regulation of prolactin secretion.